Studies of blood vessels from hypertensive animals indicate that abnormalities in contractility may be caused by alterations in Ca ions regulation. Ca ions play a number of key roles in controlling excitation and contraction of vascular smooth muscle. Therefore, a derangement in Ca ions regulation is a plausible cause of increased total peripheral resistance associated with human essential hypertension as well as many types of experimental hypertension. The objective of this investigation is to determine whether there are differences in Ca ions regulation or related enzymes between subcellular fractions from mesenteric arteries of Spontaneously Hypertensive Rats (SHR) and those fractions from normotensive rats. We have isolated from these small arteries a plasma membrane-enriched fraction that exhibits ATP-dependent CA ions transport. This fraction from normotensive rats will be compared with that from SHR with regard to CA ions uptake and release as well as certain enzymatic activities that may be related to Ca ions sequestration. These include Ca ions-ATPase, which is directly responsible for ATP-dependent Ca ions transport, (Na ion plus K ion)-ATPase, which may effect Ca ions movements across the plasma membrane by a Na ion exchange mechanism, and phosphoproteins involved in Ca ions transport. We have found that alkaline phosphatase activity of this fraction isolated from 33-day-old SHR was greater than that from normotensive rats. The proposed study will determine whether this enzyme exhibits phosphoprotein phosphatase activity and whether there are differences between normotensive and SHR in this activity. Since cyclic nucleotides may be important regulators of the above enzymes, the effect of cAMP and cGMP on their activity will also be studied. Depending on the relationship found between alterations in calcium regulation and the development of hypertension, this study will provide important information regarding either the etiology of hypertension or the effect of hypertension on blood vessels. The latter is important because hypertension is a major predisposing factor in other vascular diseases.